PMID- 10548111
OWN - NLM
STAT- MEDLINE
DCOM- 19991116
LR  - 20141120
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6755
DP  - 1999 Oct 21
TI  - NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP.
PG  - 818-22
AB  - The inhibitor-of-apoptosis (IAP) family of proteins, originally identified in
      baculoviruses, regulate programmed cell death in a variety of organisms. IAPs
      inhibit specific enzymes (caspases) in the death cascade and contain one to three
      modules of a common 70-amino-acid motif called the BIR domain. Here we describe
      the nuclear magnetic resonance structure of a region encompassing the second BIR 
      domain (BIR2) of a human IAP family member, XIAP (also called hILP or MIHA). The 
      structure of the BIR domain consists of a three-stranded antiparallel beta-sheet 
      and four alpha-helices and resembles a classical zinc finger. Unexpectedly,
      conserved amino acids within the linker region between the BIR1 and BIR2 domains 
      were found to be critical for inhibiting caspase-3. The absence or presence of
      these residues may explain the differences in caspase inhibition observed for
      different truncated and full-length IAPs. Our data further indicate that these
      residues may bind to the active site and that the BIR domain may interact with an
      adjacent site on the enzyme.
FAU - Sun, C
AU  - Sun C
AD  - Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois
      60064, USA.
FAU - Cai, M
AU  - Cai M
FAU - Gunasekera, A H
AU  - Gunasekera AH
FAU - Meadows, R P
AU  - Meadows RP
FAU - Wang, H
AU  - Wang H
FAU - Chen, J
AU  - Chen J
FAU - Zhang, H
AU  - Zhang H
FAU - Wu, W
AU  - Wu W
FAU - Xu, N
AU  - Xu N
FAU - Ng, S C
AU  - Ng SC
FAU - Fesik, S W
AU  - Fesik SW
LA  - eng
SI  - PDB/1C9Q
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amino Acids)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acids/chemistry/metabolism
MH  - Caspase 3
MH  - Caspase Inhibitors
MH  - Caspases/genetics
MH  - Enzyme Inhibitors/chemistry/pharmacology
MH  - Escherichia coli
MH  - Humans
MH  - In Vitro Techniques
MH  - Jurkat Cells
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Protein Conformation
MH  - Protein Structure, Tertiary
MH  - Proteins/*chemistry/genetics
MH  - Recombinant Proteins/chemistry/genetics
MH  - Sequence Homology, Amino Acid
MH  - X-Linked Inhibitor of Apoptosis Protein
EDAT- 1999/11/05 08:00
MHDA- 2001/03/23 10:01
CRDT- 1999/11/05 08:00
PHST- 1999/11/05 08:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/11/05 08:00 [entrez]
AID - 10.1038/44617 [doi]
PST - ppublish
SO  - Nature. 1999 Oct 21;401(6755):818-22. doi: 10.1038/44617.